ArticlePlant biotechnology journal2018
Three unrelated protease inhibitors enhance accumulation of pharmaceutical recombinant proteins in Nicotiana benthamiana.
Article in Plant biotechnology journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Nicotiana hairy roots for recombinant protein expression, where to start? A systematic review.Molecular biology reports · 2023Pooled it
- Processing and release of the maize phytocytokine Zip1.Plant physiology · 2026Article
- Nicotiana benthamiana's Responses to Agroinfiltration, a Treasure Grove of New Avenues to Improve Protein Yields in Plant Molecular Farming.Plant biotechnology journal · 2026Review
- Posttranslational modifications of heterologous proteins expressed in Nicotiana benthamiana.Plant biotechnology journal · 2026Review
- Localising enzymes to biomolecular condensates increases their accumulation and benefits engineered metabolic pathway performance in Nicotiana benthamiana.Plant biotechnology journal · 2026Article
- Molecular changes in agroinfiltrated leaves of Nicotiana benthamiana expressing suppressor of silencing P19 and coronavirus-like particles.Plant biotechnology journal · 2026Article
- 4D-DIA proteomics reveals distinct proteolytic landscapes induced by mechanical stress, Agrobacterium, and a viral capsid precursor.PloS one · 2026Article
- Silenced cutters: mechanisms and effects of protease inhibition in plant-pathogen interactions.Journal of experimental botany · 2025Review
- Expression of an antimicrobial peptide persulcatusin fused with calmodulin in rice cultured cells.Transgenic research · 2025Article
- Harnessing Transient Expression Systems with Plant Viral Vectors for the Production of Biopharmaceuticals inInternational journal of molecular sciences · 2025Review
- Papain-like cysteine proteases inFrontiers in plant science · 2025Article
- Subtilase SBT5.2 inactivates flagellin immunogenicity in the plant apoplast.Nature communications · 2024Article
- Extracellular plant subtilases dampen cold-shock peptide elicitor levels.Nature plants · 2024Article
- SBT5.2s are the major active extracellular subtilases processing IgG antibody 2F5 in the Nicotiana benthamiana apoplast.Plant biotechnology journal · 2024Article
- Bioengineering secreted proteases converts divergent Rcr3 orthologs and paralogs into extracellular immune co-receptors.The Plant cell · 2024Article
- Improving transient protein expression in agroinfiltrated Nicotiana benthamiana.The New phytologist · 2024Review
- Molecular responses of agroinfiltrated Nicotiana benthamiana leaves expressing suppressor of silencing P19 and influenza virus-like particles.Plant biotechnology journal · 2024Review
- Heterologous expression of influenza haemagglutinin leads to early and transient activation of the unfolded protein response in Nicotiana benthamiana.Plant biotechnology journal · 2024Article
- Production of Plant Proteins and Peptides with Pharmacological Potential.Advances in biochemical engineering/biotechnology · 2024Review
- Advances in Subcellular Accumulation Design for Recombinant Protein Production in Tobacco.Biodesign research · 2024Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Agroinfiltrated Nicotiana benthamiana is a flexible and scalable platform for recombinant protein (RP) production, but its great potential is hampered by plant proteases that degrade RPs. Here, we tested 29 candidate protease inhibitors (PIs) in agroinfiltrated N. benthamiana leaves for enhancing accumulation of three unrelated RPs: glycoenzyme α-Galactosidase; glycohormone erythropoietin (EPO); and IgG antibody VRC01. Of the previously described PIs enhancing RP accumulation, we found only cystatin SlCYS8 to be effective. We identified three additional new, unrelated PIs that enhance RP accumulation: N. benthamiana NbPR4, NbPot1 and human HsTIMP, which have been reported to inhibit cysteine, serine and metalloproteases, respectively. Remarkably, accumulation of all three RPs is enhanced by each PI similarly, suggesting that the mechanism of degradation of unrelated RPs follows a common pathway. Inhibitory functions HsTIMP and SlCYS8 are required to enhance RP accumulation, suggesting that their target proteases may degrade RPs. Different PIs additively enhance RP accumulation, but the effect of each PI is dose-dependent. Activity-based protein profiling (ABPP) revealed that the activities of papain-like Cys proteases (PLCPs), Ser hydrolases (SHs) or vacuolar processing enzymes (VPEs) in leaves are unaffected upon expression of the new PIs, whereas SlCYS8 expression specifically suppresses PLCP activity only. Quantitative proteomics indicates that the three new PIs affect agroinfiltrated tissues similarly and that they all increase immune responses. NbPR4, NbPot1 and HsTIMP can be used to study plant proteases and improve RP accumulation in molecular farming.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.